Prostate cancer is one of the most frequently diagnosed cancers in men globally, and its growth is often driven by male hormones called androgens. Castration Sensitive Prostate Cancer (CSPC) describes the stage where cancer cells still respond to treatments designed to lower the body’s testosterone levels. This responsiveness means the cancer can be effectively controlled by therapies that block the hormonal signals fueling tumor growth. Understanding this diagnosis and its management strategies is important for patients navigating this condition.
The Role of Androgens in Prostate Cancer Growth
The growth of most prostate cancer cells is heavily dependent on androgens, primarily testosterone. These hormones act like fuel by binding to the Androgen Receptor (AR) protein within the cell. Once bound, this complex moves to the nucleus and activates genes that promote cell division and survival. This mechanism explains why lowering circulating androgens is an effective initial treatment strategy. The cancer is considered sensitive because depriving it of hormonal fuel causes the tumor to shrink or stop growing.
Defining Castration Sensitivity and Disease Classification
Prostate cancer is classified as castration sensitive when the tumor responds to testosterone-suppressing therapies. This state is clinically defined by achieving a low serum testosterone level, known as the castrate level, typically less than 50 nanograms per deciliter (ng/dL). In CSPC, cancer activity, tracked by Prostate-Specific Antigen (PSA) levels, decreases significantly once this low testosterone level is reached. CSPC is classified based on the extent of spread. Non-metastatic CSPC (M0) means the cancer is confined to the local area or regional lymph nodes. Metastatic CSPC (mCSPC) means the cancer has spread to distant sites, such as the bones or lungs. This distinction significantly influences the treatment plan.
Core Treatment Strategy: Androgen Deprivation Therapy (ADT)
The foundation of treatment for CSPC is Androgen Deprivation Therapy (ADT), which aims to reduce testosterone to the castrate level. This approach essentially starves the cancer cells of the hormones they need to grow. ADT is achieved through two main methods: medical castration or surgical castration.
Medical castration involves using Luteinizing Hormone-Releasing Hormone (LHRH) agonists or antagonists, typically administered via injection, to block androgen production by the testicles. Surgical castration, known as a bilateral orchiectomy, involves the removal of the testicles, which are the main source of testosterone production. Both methods aim to reduce circulating testosterone below 50 ng/dL.
ADT is associated with a range of side effects due to the systemic reduction of male hormones. Common side effects include hot flashes, fatigue, decreased libido, and erectile dysfunction. Longer-term effects may include loss of bone density, increasing the risk of fractures, and metabolic changes like weight gain and increased risk of diabetes. Managing these adverse effects is a key part of long-term care.
Treatment Intensification: Combining ADT with Systemic Therapies
For patients diagnosed with metastatic CSPC (mCSPC), the standard of care has evolved beyond ADT monotherapy to a strategy of treatment intensification. This involves combining ADT with other systemic agents to achieve a deeper and more durable response. This combination approach has been shown to improve overall survival compared to ADT alone, particularly for those with high-volume or aggressive disease.
Chemotherapy
One common intensification strategy involves adding chemotherapy, specifically docetaxel, to the ADT regimen. Docetaxel works by interfering with cell division, offering a non-hormonal mechanism to attack the cancer cells early in the disease course. Clinical trials demonstrated that this combination provides a significant survival benefit when administered shortly after the mCSPC diagnosis.
Novel Hormonal Agents
The other primary method of intensification is the addition of novel hormonal agents, known as Androgen Receptor Pathway Inhibitors (ARPIs). These include drugs like abiraterone, enzalutamide, apalutamide, and darolutamide. These agents work through different mechanisms than conventional ADT, either by blocking residual androgen production outside the testicles (abiraterone) or by more effectively blocking the androgen receptor itself. Current guidelines often recommend combining ADT with one of these novel ARPIs for mCSPC. In specific cases, a “triplet therapy” involving ADT, an ARPI, and docetaxel chemotherapy may be used to maximize the initial anti-cancer effect.
Monitoring Disease Response and Defining Progression
Monitoring treatment effectiveness in CSPC primarily involves regular blood tests, especially for Prostate-Specific Antigen (PSA) levels, and periodic imaging scans. A successful response to ADT and any combination therapy is indicated by a rapid and significant drop in the PSA level. The lowest PSA achieved during treatment, known as the PSA nadir, is an important prognostic marker, with lower levels often associated with better long-term outcomes.
Imaging studies, such as CT scans and bone scans, are used at the time of diagnosis to determine the extent of metastatic disease and are repeated if new symptoms arise. The primary goal of monitoring is to detect when the cancer stops responding to the current hormonal therapy.
The definition of treatment failure is progression to Castration Resistant Prostate Cancer (CRPC). This transition occurs when the cancer begins to grow again despite the patient maintaining castrate levels of testosterone (below 50 ng/dL).
Progression to CRPC is typically diagnosed by three consecutive rises in PSA levels, or by new or worsening disease visible on imaging scans, while testosterone remains suppressed. At this point, the disease is reclassified and requires a shift to different treatment strategies.